Diseases of the Pancreas Flashcards
Glasgow criteria for prognosis in acute pancreatitis
• Age > 55 years
• P O 2 < 8 kPa (60 mmHg)
• White blood cell count > 15 × 10 9 /L
• Albumin < 32 g/L (3.2 g/dL)
• Serum calcium < 2 mmol/L (8 mg/dL) (corrected)
• Glucose > 10 mmol/L (180 mg/dL)
• Urea > 16 mmol/L (45 mg/dL) (after rehydration)
• Alanine aminotransferase > 200 U/L
• Lactate dehydrogenase > 600 U/L
Initial assessment that predicts severe pancreatitis
• Clinical impression of severity
• Body mass index > 30 kg/m 2
• Pleural effusion on chest X-ray
• APACHE II score > 8
Features that predict severe pancreatitis at 24 hours after admission
• Clinical impression of severity
• APACHE II score > 8
• Glasgow score > 3
• Persisting organ failure, especially if multiple
• CRP > 150 mg/L
Features that predict severe pancreatitis at 48 hours after admission
• Clinical impression of severity
• Glasgow score > 3
• CRP > 150 mg/L
• Persisting organ failure for 48 hours
• Multiple or progressive organ failure
Pathophysiology of acute pancreatitis
-Autodigestion of pancreatic tissue by the pancreatic enzymes, leading to necrosis
-Pancreatic duct obstruction (common bile duct stones, tumours)
-Reflux of bile or duodenal contents into pancreatic ducts (sphincter of Oddi dysfunction)
-Hyperstimulation of pancreas (alcohol, triglycerides)
-Defective intracellular transport and secretion of pancreatic zymogens
Triggers of acute pancreatitis
-Alcohol
-Gallstones
-Pancreatic duct obstruction
Common causes of acute pancreatitis
• Gallstones
• Alcohol
• Idiopathic causes
• Post-ERCP (endoscopic retrograde cholangiopancreatography)
Rare causes of acute pancreatitis
• Post-surgical (abdominal, cardiopulmonary bypass)
• Trauma
• Drugs (azathioprine/mercaptopurine, thiazide diuretics, sodium valproate)
• Metabolic (hypercalcaemia, hypertriglyceridaemia)
• Pancreas divisum
• Sphincter of Oddi dysfunction
• Infection (mumps, Coxsackie virus)
• Hereditary factors
• Renal failure
• Organ transplantation (kidney, liver)
• Severe hypothermia
• Petrochemical exposure
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Gallstones
Ethanol
Trauma
Steroids
Mumps (other viruses include Coxsackie B)
Autoimmune (e.g. polyarteritis nodosa) Ascaris infection
Scorpion venom
Hypertriglyceridaemia, Hyperchylomicronaemia, Hypercalcaemia, Hypothermia
ERCP
Drugs (azathioprine, mesalazine*, didanosine, bendroflumethiazide, furosemide, pentamidine, steroids, sodium valproate)
Clinical features of acute pancreatitis
-Severe, constant upper epigastric pain, of increasing intensity over 15–60 minutes, which radiates to the back.
-Nausea and vomiting are common.
-Marked epigastric tenderness, but in the early stages, guarding and rebound tenderness are absent because the inflammation is principally retroperitoneal.
-Bowel sounds become quiet or absent as paralytic ileus develops.
-In severe cases, the patient becomes hypoxic and develops hypovolaemic shock with oliguria.
-Discoloration of the flanks (Grey Turner’s sign) or the periumbilical region (Cullen’s sign) is a feature of severe pancreatitis with haemorrhage.
-Low grade fever
-Rarely, ischaemic Purtscher retinopathy: temporary or permanent blindness
Differential diagnosis of acute pancreatitis
-Perforated viscus
-Acute cholecystitis
-Myocardial infarction
Pancreatic complications of acute pancreatitis
-Necrosis
=Non-viable pancreatic tissue and peripancreatic tissue death; frequently infected
-Pseudocyst
=Disruption of pancreatic ducts
=Walled with granulation or fibrous tissue, 4+ weeks after attack, mostly retrogastric, elevate amylase, CT ERCP MRI USS, observed for 12 weeks as 50% resolve
=Endoscopic or surgical cystogastromy or aspiration
-Pancreatic ascites or pleural effusion
=disruption of pancreatic ducts
-Abscess
=Circumscribed collection of pus close to the pancreas and containing little or no pancreatic necrotic tissue
=Transgastric drainage is one method of treatment, endoscopic drainage is an alternative
-Peripancreatic fluid collections
=25%, lack wall of granulation or fibrous tissue, may resolve or develop into pseudocysts or abscesses, avoid aspiration and drainage
-Haemorrhage
=Infected necrosis may involve vascular structures with resultant haemorrhage that may occur de novo or as a result of surgical necrosectomy.
=When retroperitoneal haemorrhage occurs Grey Turner’s sign may be identified
Systemic complications of acute pancreatitis
-Systemic inflammatory response syndrome (SIRS/ ARDS)
=Increased vascular permeability from cytokine, platelet-aggregating factor and kinin release
-Hypoxia
=Acute respiratory distress syndrome (ARDS) due to microthrombi in pulmonary vessels
-Hyperglycaemia
=Disruption of islets of Langerhans with altered insulin/glucagon release
-Hypocalcaemia
=Sequestration of calcium in fat necrosis, fall in ionised calcium
-Reduced serum albumin concentration
=Increased capillary permeability
GI complications of acute pancreatitis
-Upper gastrointestinal bleeding
=Gastric or duodenal erosions
-Variceal haemorrhage
=Splenic or portal vein thrombosis
-Erosion into colon
=Erosion by pancreatic pseudocyst
-Duodenal obstruction
=Compression by pancreatic mass
-Obstructive jaundice
=Compression of common bile duct
Describe pancreatic pseudocysts
-Pancreatic fluid collection= A collection of fluid and debris may develop in the lesser sac, following inflammatory rupture of the pancreatic duct
-It is initially contained within a poorly defined, fragile wall of granulation tissue, which matures over a 6-week period to form a fibrous capsule.
-Such ‘pseudocysts’ are common and usually asymptomatic, resolving as the pancreatitis recovers.
-Pseudocysts greater than 6 cm in diameter seldom disappear spontaneously and can cause constant abdominal pain and compress or erode surrounding structures, including blood vessels, to form pseudoaneurysms.
-Large pseudocysts can be detected clinically as a palpable abdominal mass.
How does pancreatic ascites occur?
-Fluid leaks from a disrupted pancreatic duct into the peritoneal cavity.
-Leakage into the thoracic cavity can result in a pleural effusion or a pleuro-pancreatic fistula.
Investigations of acute pancreatitis
-Raised serum amylase (>x3 normal) or lipase useful for late presentations >24 hours) concentrations and ultrasound or CT evidence of pancreatic swelling.
=a diagnosis of acute pancreatits can be made without imaging if characteristic pain + amylase/lipase > 3 times normal level
=however, early ultrasound imaging is important to assess the aetiology as this may affect management - e.g. patients with gallstones/biliary obstruction
=other options include contrast-enhanced CT
-Plain X-rays exclude perforation or obstruction and identify pulmonary complications.
-Amylase concentrations may have returned to normal if measured 24–48 hours after onset
-A persistently elevated serum amylase concentration suggests pseudocyst formation
-Peritoneal amylase concentrations are massively elevated in pancreatic ascites.
-Serum lipase measurements =greater diagnostic accuracy for acute pancreatitis.
-Ultrasound to confirm diagnosis, although in the earlier stages the gland may not be grossly swollen.
-Contrast-enhanced pancreatic CT performed 6–10 days after admission can be useful in assessing viability of the pancreas if persisting organ failure, sepsis or clinical deterioration is present (pancreatic necrosis)
=Decreased pancreatic enhancement
=Gas suggests infection and impending abscess formation, in which case percutaneous aspiration of material for bacterial culture should be carried out and appropriate antibiotics prescribed
Management of acute pancreatitis
-Fluid resuscitation
=Aggressive early hydration with crystalloids. In severe cases 3-6 litres of third space fluid loss may occur
=Aim for a urine output of > 0.5mls/kg/hr
=May also help relieve pain by reducing lactic acidosis
-Analgesia
=Pain may be severe so this is a key priority of care
=Intravenous opioids are normally required to adequately control the pain
-Nutrition
=Patients should not routinely be made ‘nil-by-mouth’ unless there is a clear reason e.g. the patient is vomiting
=Enteral nutrition should be offered to anyone with moderately severe or severe acute pancreatitis within 72 hours of presentation
=Parental nutrition should only be used if enteral nutrition has failed or is contraindicated
-Role of antibiotics
=NICE state the following: ‘Do not offer prophylactic antimicrobials to people with acute pancreatitis’
=Potential indications include infected pancreatic necrosis
-Role of surgery
=Patients with acute pancreatitis due to gallstones should undergo early cholecystectomy
=Patients with obstructed biliary system due to stones should undergo early ERCP
=Patients who fail to settle with necrosis and have worsening organ dysfunction may require debridement, fine needle aspiration is still used by some
=Patients with infected necrosis should undergo either radiological drainage or surgical necrosectomy. The choice of procedure depends upon local expertise
Management in ITU for acute pancreatitis
-Opiate analgesics
-Hypovolaemia corrected using normal saline/ other crystalloids.
-Central venous line and urinary catheter= monitor patients with shock.
-Oxygen for hypoxic patients,
-SIRS= ventilatory support
-Hyperglycaemia corrected using insulin
-Hypocalcaemia by intravenous calcium injection.
-Nasogastric aspiration= paralytic ileus
-Enteral feeding in severely catabolic state
=Decreases endotoxaemia and reduce systemic complications.
-Prophylaxis of thromboembolism with subcutaneous low-molecular-weight heparin
-Infected necrosis is treated with antibiotics that penetrate necrotic tissue
Management of patients who present with cholangitis or jaundice (in association with severe acute pancreatitis)
-Urgent ERCP to diagnose and treat choledocholithiasis.
-Biliary imaging (using MRCP or EUS) can be carried out after the acute phase has resolved.
-If LFTs return to normal and ultrasound has not demonstrated a dilated biliary tree, laparoscopic cholecystectomy
-Cholecystectomy should be undertaken within 2 weeks of resolution of pancreatitis
-Patients with infected pancreatic necrosis or pancreatic abscess require urgent endoscopic drainage or minimally invasive retroperitoneal pancreatic (MIRP) necrosectomy to debride all cavities of necrotic material.
-Pancreatic pseudocysts can be treated by drainage into the stomach or duodenum.
Describe chronic pancreatitis
-Chronic inflammatory disease characterised by
=fibrosis
=destruction of exocrine pancreatic tissue.
-Diabetes mellitus occurs in advanced cases because the islets of Langerhans are involved
Causes of chronic pancreatitis- TIGARO
-Toxic-metabolic
-Idiopathic (tropical/ early-late onset
-Genetic (CF, haemochromatosis)
-Autoimmune
-Recurrent and severe acute pancreatitis (post-necrotic)
-Obstructive (ductal, tumours, stones, structural)
Around 80% of cases are due to alcohol excess with up to 20% of cases being unexplained.
Toxic-metabolic causes of chronic pancreatitis
-Alcohol
-Tobacco
-Hypercalcaemia
-CKD
Genetic causes of chronic pancreatitis
-Hereditary pancreatitis (cationic trypsinogen mutation)
-SPINK-1 mutation
-Cystic fibrosis
Obstructive causes of chronic pancreatitis
-Ductal adenocarcinoma
-Intraductal papillary mucinous neoplasia
-Pancreas dividum
-Sphincter of Oddi stenosis
Mechanisms of chronic pancreatitis
-Oxidative stress
-Toxic-metabolic
-Necrosis-fibrosis
-Recurrent acute pancreatitis
-Duct obstruction
Clinical features of chronic pancreatitis
-Middle-aged alcoholic men
-Almost all present with abdominal pain.
-In 50%, this occurs as episodes of ‘acute pancreatitis’
-Relentless, slowly progressive chronic pain without acute exacerbations affects 35% of patients, while the remainder have no pain but present with diarrhoea.
-Pain is due to a combination of increased pressure within the pancreatic ducts and direct involvement of peripancreatic nerves by the inflammatory process.
=Relieved by leaning forwards or by drinking alcohol, worse 15-30 minutes after meal
-Weight loss is common and results from a combination of anorexia, avoidance of food because of post-prandial pain, malabsorption and/or diabetes.
=Steatorrhoea occurs when more than 90% of the exocrine tissue has been destroyed; protein malabsorption develops only in the most advanced cases. 5-25 years after pain onset
-Overall, 30% of patients have (secondary) diabetes but this figure rises to 70% in those with chronic calcific pancreatitis. 20 years later
-Physical examination reveals a thin, malnourished patient with epigastric tenderness.
=Skin pigmentation over the abdomen and back is common and results from chronic use of a hot water bottle (erythema ab igne).
=Many patients have features of other alcohol- and smoking-related diseases.
Complications of chronic pancreatitis
• Pseudocysts and pancreatic ascites, which occur in both acute and chronic pancreatitis
• Obstructive jaundice due to benign stricture of the common bile duct as it passes through the diseased pancreas
• Duodenal stenosis
• Portal or splenic vein thrombosis leading to segmental portal hypertension and gastric varices
• Peptic ulcer
Investigations of chronic pancreatitis
-Tests to establish the diagnosis
• Ultrasound
• Computed tomography (may show atrophy, calcification or ductal dilatation)
• Abdominal X-ray (may show calcification)
• Magnetic resonance cholangiopancreatography
• Endoscopic ultrasound
-Tests to define pancreatic function
• Collection of pure pancreatic juice after secretin injection (gold standard but invasive and seldom used)
• Pancreolauryl test
• Faecal pancreatic elastase
-Tests to demonstrate anatomy prior to surgery
• Magnetic resonance cholangiopancreatography
Intervention in chronic pancreatitis
-Endoscopic therapy
• Dilatation or stenting of pancreatic duct strictures
• Removal of calculi (mechanical or shock-wave lithotripsy)
• Drainage of pseudocysts
-Surgical methods
• Partial pancreatic resection, preserving the duodenum
• Pancreatico-jejunostomy
Management of chronic pancreatitis
-Alcohol misuse= avoidance
-Pain relief
=NSAIDs
=Opiates
=Pregabalin and tricyclic antidepressants at low dose
=Oral pancreatic enzyme supplements suppress pancreatic secretion- reduces analgesic consumption
-Malabsorption
=Dietary fat restriction (with supplementary medium-chain triglyceride therapy in malnourished patients)
=PPI optimised duodenal pH for pancreatic enzyme activity
Describe autoimmune pancreatitis
-Form of chronic pancreatitis that can mimic cancer, but which responds to glucocorticoids.
-Characterised by abdominal pain, weight loss or obstructive jaundice, without acute attacks of pancreatitis.
-Increased serum IgG or IgG4 and the presence of other autoantibodies.
-Imaging= diffusely enlarged pancreas, narrowing of the pancreatic duct and stricturing of the lower bile duct.
-AIP may occur alone or with other autoimmune disorders, such as Sjögren’s syndrome, primary sclerosing cholangitis or IBD.
-The response to glucocorticoids is usually excellent but some patients require azathioprine.
Describe adenocarcinomas of the pancreas
-80/90% pancreatic neoplasms arising from pancreatic duct, typically at the head of the pancreas
-Involve local structures and metastasise to regional lymph nodes
-Advanced disease at time of presentation non-specific presentation
-Men x2
-Associated with increasing age, smoking, chronic pancreatitis
-5-10% patients’ genetic predisposition
-Survival 3-5%
-6-10 months locally advanced disease, 3-5 months with metastases
Genetic predisposition to adenocarcinoma of the pancreas
-Hereditary pancreatitis
-HNPCC
-Familial atypical mole multiple melanoma syndrome (FAMMM)
Associations with pancreatic cancer
-Increasing age
-Smoking
-Diabetes
-Chronic pancreatitis (alcohol does not appear an independent risk factor though)
-Hereditary non-polyposis colorectal carcinoma
-Multiple endocrine neoplasia
-BRCA2 gene
-KRAS gene mutation
Neuro-endocrine tumour of pancreas
-Grow more slowly
-Better prognosis
Clinical features of adenocarcinoma of pancreas
-Asymptomatic until advanced stage
=Central epigastric abdominal pain (invasion of coeliac plexus, incessant and gnawing, radiates from upper abdomen to back, eased by bending forward)
=Weight loss, anorexia
=Obstructive painless jaundice (involvement of common bile duct, with severe pruritus)- pale stools, dark urine, pruritis, cholestatic LFT
-Some diarrhoea, vomiting from duodenal obstruction, DM, recurrent venous thrombosis, acute pancreatitis or depression
=Trousseau sign (migratory thrombophlebitis)
=Steatorrhoea (loss of exocrine function)
=DM (loss of endocrine)
=Atypical back pain
-Physical Examination
=Weight loss
=Abdominal mass due to tumour itself (hepatomegaly from mets, palpable gallbladder, epigastric mass)
=Courvoisier’s sign: palpable gallbladder in jaundice consequence of distal biliary obstruction by a pancreatic cancer
Investigations of adenocarcinoma of the pancreas
-Ultrasound and contrast-enhanced high resolution CT first line is diagnosis suspected
=Double duct sign (dilation)
-EUS/laparoscopy with ultrasound defines tumour size, involvement of blood vessels and metastatic spread
-MRCP, ERCP (relieve obstructive jaundice)
Management of adenocarcinoma of the pancreas
-Surgical resection= 5-year survival 12%: Whipples (results in dumping syndrome, peptic ulcer disease)
-Improved survival with adjuvant chemotherapy using gemcitabine
-ERCP with stenting for palliation
-Only 10-15% resectable as locally advanced
-Palliative
=Analgesics/ coeliac plexus neurolysis
Incidental pancreatic masses
-Cystic neoplasms
=rarely malignant and do not require surgery
=Mucinous cysts more in women usually in pancreatic tail
=Aspiration, measuring CEA and amylase concentrations determine mucinous or not
-Mucinous lesions resected
-Intraductal papillary mucinous neoplasia (IPMN)
=elderly men
=main pancreatic duct with marked dilation and plugs of mucous
=pre-malignant but indolent condition
